Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs

Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs
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DOI:
10.1016/j.jtcvs.2009.10.002
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发表时间:
2010-02-01
影响因子:
6
通讯作者:
Macchiarini, Paolo
Macchiarini, Paolo
中科院分区:
医学1区
文献类型:
--
作者:
Go, Tetsuhiko;Jungebluth, Philipp;Macchiarini, Paolo

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目的:我们试图确定上皮细胞和间充质干细胞衍生的软骨细胞对猪组织工程气道移植存活的相对贡献。方法:采用洗涤酶法制备非免疫原性气管基质。主要组织相容性复合物不匹配的动物(体重65 +/- 4 kg)分为4组(每组n = 5),气管6cm处仅用脱细胞基质(I组)、外用自体间充质干细胞衍生软骨细胞的脱细胞基质(II组)、内用自体上皮细胞的脱细胞基质(III组)或两种细胞类型的脱细胞基质(IV组)原位置换。自体细胞恢复、培养和扩增。利用生长因子将间充质干细胞分化为软骨细胞。两种细胞类型在双室生物反应器中同时接种。在整个研究过程中,动物没有受到免疫抑制。连续从受者身上采集活检标本和血液样本,对动物进行最长60天的观察。结果:两种细胞在72小时内完全覆盖基质。各组对猪的成活率有显著影响(P
Objective: We sought to determine the relative contributions of epithelial cells and mesenchymal stem cell-derived chondrocytes to the survival of tissue-engineered airway transplants in pigs.Methods: Nonimmunogenic tracheal matrices were obtained by using a detergent-enzymatic method. Major histocompatibility complex-unmatched animals (weighing 65 +/- 4 kg) were divided into 4 groups (each n = 5), and 6 cm of their tracheas were orthotopically replaced with decellularized matrix only (group I), decellularized matrix with autologous mesenchymal stem cell-derived chondrocytes externally (group II), decellularized matrix with autologous epithelial cells internally (group III), or decellularized matrix with both cell types (group IV). Autologous cells were recovered, cultured, and expanded. Mesenchymal stem cells were differentiated into chondrocytes by using growth factors. Both cell types were seeded simultaneously with a dual-chamber bioreactor. Animals were not immunosuppressed during the entire study. Biopsy specimens and blood samples were taken from recipients continuously, and animals were observed for a maximum of 60 days.Results: Matrices were completely covered with both cell types within 72 hours. Survival of the pigs was significantly affected by group (P